Quinolinic acid-induced lesions of the rat striatum: quantitative autoradiographic binding assessment.
Injection of the excitatory amino-acid analog quinolinic acid into the striatum of rats produces neuropathological and neurochemical alterations that are reminiscent of those observed in Huntington's disease. In the present study, we evaluated quinolinic acid-induced striatal changes using quantitative autoradiographic binding assays for [3H]MK-801-labeled NMDA receptors, [3H]SCH 23390-labeled dopamine D1 and [3H]sulpiride-labeled dopamine D2 receptors, [3H]CGS 21680-labeled adenosine A2a receptors, [3H]mazindol-labeled dopamine uptake sites, [3H]hemicholinium-3-labeled high affinity choline uptake sites and [3H]PK 11195-labeled peripheral-type benzodiazepine binding sites, as markers of different cellular populations of the striatum. We found that decrease in [3H]MK 801 and [3H]SCH 23390 binding, and increase in [3H]PK 11195 binding were the most significant alterations induced by the intrastriatal injection of quinolinic acid. Concentrations of [3H]CGS 21680 and [3H]hemicholinium-3 bindings were also decreased, however, to a lesser extent, and [3H]sulpiride binding was not significantly affected. Quinolinic acid also produced an increase in [3H]mazindol binding. We tested the specificity of the N-methyl-D-aspartate receptor-mediated mechanism of quinolinic acid neurotoxicity using MK 801 pretreatment, an N-methyl-D-aspartate receptor antagonist, and it prevented all quinolinic acid-induced binding changes. Because anticholinergic drugs were proposed to prevent the neurotoxic side-effects of MK 801, we also tested the effect of scopolamine pretreatment and found that it altered neither the neurotoxicity induced by quinolinic acid nor the neuroprotective effect of MK 801.
Levivier
M
M
Department of Neurology, Columbia University, New York, USA.
Przedborski
S
S
D000818:Animals; D001345:Autoradiography / Q000379:methods*; D001552:Benzazepines / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D018678:Cholinergic Agents / Q000494:pharmacology; D003342:Corpus Striatum / Q000473:pathology*; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006426:Hemicholinium 3 / Q000494:pharmacology; D006816:Huntington Disease / Q000473:pathology*; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D008454:Mazindol / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000737:chemistry / Q000187:drug effects; D017378:Quinolinic Acid / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012601:Scopolamine / Q000494:pharmacology; D013469:Sulpiride / Q000494:pharmacology; D014316:Tritium
D001552:Benzazepines; D018678:Cholinergic Agents; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D018691:Excitatory Amino Acid Antagonists; D007546:Isoquinolines; D018727:Muscarinic Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D014316:Tritium; D006426:Hemicholinium 3; D016291:Dizocilpine Maleate; D013469:Sulpiride; D008454:Mazindol; D012601:Scopolamine; D017378:Quinolinic Acid; C037850:PK 11195